Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma
Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy of the mucosal epithelium of the oral cavity, pharynx, and larynx. Laryngeal squamous cell carcinoma (LSCC) and oral squamous cell carcinoma are common HNSCC subtypes. Patients with metastatic HNSCC have a poor prognosi...
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Frontiers Media S.A.
2022-08-01
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.884590/full |
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author | Chao Huang Chao Huang Yun Liang Yun Liang Yi Dong Yi Dong Li Huang Anlei Li Ran Du Ran Du Hao Huang Hao Huang Hao Huang Hao Huang |
author_facet | Chao Huang Chao Huang Yun Liang Yun Liang Yi Dong Yi Dong Li Huang Anlei Li Ran Du Ran Du Hao Huang Hao Huang Hao Huang Hao Huang |
author_sort | Chao Huang |
collection | DOAJ |
description | Background: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy of the mucosal epithelium of the oral cavity, pharynx, and larynx. Laryngeal squamous cell carcinoma (LSCC) and oral squamous cell carcinoma are common HNSCC subtypes. Patients with metastatic HNSCC have a poor prognosis. Therefore, identifying molecular markers for the development and progression of HNSCC is essential for improving early diagnosis and predicting patient outcomes.Methods: Gene expression RNA-Seq data and patient clinical traits were obtained from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) and Gene Expression Omnibus databases. Differentially expressed gene (DEG) screening was performed using the TCGA-HNSC dataset. Intersection analysis between the DEGs and a list of core matrisome genes obtained from the Matrisome Project was used to identify differentially expressed matrisome genes. A prognostic model was established using univariate and multivariate Cox regression analyses, least absolute shrinkage, and selection operator (LASSO) regression analysis. Immune landscape analysis was performed based on the single-sample gene set enrichment analysis algorithm, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, prognostic value, receiver operating characteristic curve analysis, and gene mutation analyses. Immunohistochemical results regarding prognostic protein levels were obtained from the Human Protein Atlas. Single-gene RNA-sequencing data were obtained from GSE150321 and GSE172577 datasets. CCK-8 and Transwell assays were used to confirm cell proliferation and migration.Results: A total of 1,779 DEGs, including 939 upregulated and 840 downregulated genes, between tumor and normal samples were identified using the TCGA-HNSC microarray data. Intersection analysis revealed 52 differentially expressed matrisome-related genes. After performing univariate and multivariate Cox regression and LASSO analyses, a novel prognostic model based on six matrisome genes (FN1, LAMB4, LAMB3, DMP1, CHAD, and MMRN1) for HNSCC was established. This risk model can successfully predict HNSCC survival. The high-risk group had worse prognoses and higher enrichment of pathways related to cancer development than the low-risk group. Silencing LAMB4 in HNSCC cell lines promoted cell proliferation and migration.Conclusion: This study provides a novel prognostic model for HNSCC. Thus, FN1, LAMB4, LAMB3, DMP1, CHAD, and MMRN1 may be the promising biomarkers for clinical practice. |
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spelling | doaj.art-883562931421423c99c76807ce1bb70a2022-12-22T04:01:08ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-08-011010.3389/fcell.2022.884590884590Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinomaChao Huang0Chao Huang1Yun Liang2Yun Liang3Yi Dong4Yi Dong5Li Huang6Anlei Li7Ran Du8Ran Du9Hao Huang10Hao Huang11Hao Huang12Hao Huang13Department of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, ChinaDepartment of Otolaryngology-Head and Neck Surgery, Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, ChinaDepartment of Nephrology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Cell Biology, School of Life Sciences, Central South University, Changsha, ChinaHunan Key Laboratory of Organ Fibrosis, Central South University, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, ChinaBackground: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy of the mucosal epithelium of the oral cavity, pharynx, and larynx. Laryngeal squamous cell carcinoma (LSCC) and oral squamous cell carcinoma are common HNSCC subtypes. Patients with metastatic HNSCC have a poor prognosis. Therefore, identifying molecular markers for the development and progression of HNSCC is essential for improving early diagnosis and predicting patient outcomes.Methods: Gene expression RNA-Seq data and patient clinical traits were obtained from The Cancer Genome Atlas-Head and Neck Squamous Cell Carcinoma (TCGA-HNSC) and Gene Expression Omnibus databases. Differentially expressed gene (DEG) screening was performed using the TCGA-HNSC dataset. Intersection analysis between the DEGs and a list of core matrisome genes obtained from the Matrisome Project was used to identify differentially expressed matrisome genes. A prognostic model was established using univariate and multivariate Cox regression analyses, least absolute shrinkage, and selection operator (LASSO) regression analysis. Immune landscape analysis was performed based on the single-sample gene set enrichment analysis algorithm, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, prognostic value, receiver operating characteristic curve analysis, and gene mutation analyses. Immunohistochemical results regarding prognostic protein levels were obtained from the Human Protein Atlas. Single-gene RNA-sequencing data were obtained from GSE150321 and GSE172577 datasets. CCK-8 and Transwell assays were used to confirm cell proliferation and migration.Results: A total of 1,779 DEGs, including 939 upregulated and 840 downregulated genes, between tumor and normal samples were identified using the TCGA-HNSC microarray data. Intersection analysis revealed 52 differentially expressed matrisome-related genes. After performing univariate and multivariate Cox regression and LASSO analyses, a novel prognostic model based on six matrisome genes (FN1, LAMB4, LAMB3, DMP1, CHAD, and MMRN1) for HNSCC was established. This risk model can successfully predict HNSCC survival. The high-risk group had worse prognoses and higher enrichment of pathways related to cancer development than the low-risk group. Silencing LAMB4 in HNSCC cell lines promoted cell proliferation and migration.Conclusion: This study provides a novel prognostic model for HNSCC. Thus, FN1, LAMB4, LAMB3, DMP1, CHAD, and MMRN1 may be the promising biomarkers for clinical practice.https://www.frontiersin.org/articles/10.3389/fcell.2022.884590/fullhead and neck squamous cell carcinomadifferentially expressed genescore matrisome geneextracellular matrixsingle-cell analysisLAMB4 |
spellingShingle | Chao Huang Chao Huang Yun Liang Yun Liang Yi Dong Yi Dong Li Huang Anlei Li Ran Du Ran Du Hao Huang Hao Huang Hao Huang Hao Huang Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma Frontiers in Cell and Developmental Biology head and neck squamous cell carcinoma differentially expressed genes core matrisome gene extracellular matrix single-cell analysis LAMB4 |
title | Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma |
title_full | Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma |
title_fullStr | Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma |
title_full_unstemmed | Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma |
title_short | Novel prognostic matrisome-related gene signature of head and neck squamous cell carcinoma |
title_sort | novel prognostic matrisome related gene signature of head and neck squamous cell carcinoma |
topic | head and neck squamous cell carcinoma differentially expressed genes core matrisome gene extracellular matrix single-cell analysis LAMB4 |
url | https://www.frontiersin.org/articles/10.3389/fcell.2022.884590/full |
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